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Myo5a  -  myosin VA

Mus musculus

Synonyms: 9630007J19Rik, AI413174, AI661011, Dbv, Dilute, ...
 
 
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Disease relevance of Myo5a

  • In the present report, we evaluated the effect of overexpression of these mutants on melanosome, melanophilin, and myosin-Va localization in B16 melanoma cells [1].
  • Expression of constructs of the neuronal isoform of myosin-Va interferes with the distribution of melanosomes and other vesicles in melanoma cells [2].
  • Myosin Va and microtubule-based motors are required for fast axonal retrograde transport of tetanus toxin in motor neurons [3].
 

Psychiatry related information on Myo5a

 

High impact information on Myo5a

  • Here we report that the Griscelli disease locus co-localizes on chromosome 15q21 with the myosin-Va gene, MYO5a, and that mutations of this gene occur in two patients with the disease [6].
  • Genetic studies of mouse melanocytes allowed the discovery of essential elements involved in organelle transport including the myosin-Va motor and its receptor and adaptor molecules on the organelle surface [7].
  • Here we show that an actin-based vesicle-transport motor, MyoVA, can interact directly with a microtubule-based transport motor, KhcU [8].
  • Rab27a binds to the melanosome first and then recruits melanophilin, which in turn recruits myosin-Va [9].
  • Melanophilin creates this link by binding to Rab27a in a GTP-dependent fashion through its amino terminus, and to myosin-Va through its carboxy terminus [9].
 

Biological context of Myo5a

  • The occurrence of homozygous-viable dilute-short ear (Myo5a-Bmp5) double mutants in mouse specific locus mutation experiments has generally been assumed to be the result of double non-disjunction such that the mutant inherits two copies of chromosome 9 carrying the recessive alleles from the test-stock [10].
  • Dilute-opisthotonus (dop) is a spontaneous gene mutation in the rat, and phenotypes of the homozygote (dop/dop) are similar to those of the Myo5a-deficient mouse, suggesting that the mutation resides in the rat Myo5a gene [11].
  • An intragenic rearrangement consisting of a 306-bp inversion associated with 17-bp and 217-bp deletions were identified in the Myo5a gene of the dop genome [11].
  • Loss of heterozygosity at the dilute-short ear (Myo5a-Bmp5) region of the mouse: mitotic recombination or double non-disjunction [10]?
  • These results identify myosin Va as a neurofilament-associated protein, and show that this association is essential to establish the normal distribution, axonal transport, and content of myosin Va, and the proper numbers of neurofilaments in axons [12].
 

Anatomical context of Myo5a

  • One interpretation of these observations is that Rab27a functions wholly or in part as the melanosome receptor for myosin Va (Myo5a) [13].
  • Melanophilin and myosin Va track the microtubule plus end on EB1 [14].
  • The flailer protein, which is expressed predominantly in brain, contains the N-terminal 83 amino acids of Gnb5 fused in-frame with the C-terminal 711 amino acids of MyoVA, including the globular tail domain that binds organelles for intracellular transport [15].
  • Biochemical and genetic studies indicate that the flailer protein competes with wild-type MyoVA in vivo, preventing the localization of smooth endoplasmic reticulum vesicles in the dendritic spines of cerebellar Purkinje cells [15].
  • In leaden melanocytes permeabilized before fixation, myosin-Va immunoreactivity was greatly attenuated, suggesting that myosin-Va is free in the cytoplasm [16].
 

Associations of Myo5a with chemical compounds

  • The behavioral and convulsant effects of pefloxacin (PEFLO), a quinolone derivative, were studied after intraperitoneal (i.p.) administration to Dilute Brown Agouti DBA/2J (DBA/2) mice, a strain genetically susceptible to sound-induced seizures [17].
  • Gabapentin (1-50 mg/kg, intraperitoneally (i.p.)) was able to antagonize audiogenic seizures in Dilute Brown Agouti DBA2J (DBA/2) mice in a dose-dependent manner [18].
  • We also show that the membrane of vesicles co-fractionated with intact manchettes by sucrose gradient ultracentrifugation display immunogold-labeled myosin Va [19].
  • Glutamate receptor targeting in the postsynaptic spine involves mechanisms that are independent of myosin Va [20].
  • These results suggest that the tail and neck domain play a role in the Ca(2+) dependent regulation of myosin Va [21].
 

Physical interactions of Myo5a

  • Although Slac2-a directly interacts with Rab27A and myosin Va via its N-terminal region (amino acids 1 to 146) and the middle region (amino acids 241 to 405), respectively, the functional importance of the putative actin-binding domain of the Slac2-a C terminus (amino acids 401 to 590) in melanosome transport has never been elucidated [22].
  • We show that myosin Va binding does not induce the global folding of melanophilin [23].
 

Other interactions of Myo5a

  • Melanophilin, the product of the leaden locus, is required for targeting of myosin-Va to melanosomes [16].
  • Systematic analysis of the mRNA and protein distribution of these myosins indicates that Myo5a is most abundant in brain, whereas Myo5b and Myo5c are expressed chiefly in non-neuronal tissues [24].
  • A homozygous viable Myo5a-Bmp5 double mutant was recovered recently in our laboratory [10].
  • In the Hrb mutant, myosin-Va-bound proacrosome vesicles tether to the acroplaxome, where they flatten and form a flat sac, designated pseudoacrosome [25].
  • Immunoelectron microscopy, coimmunoprecipitation, and blot overlay analyses demonstrate that myosin Va in axons associates with neurofilaments, and that the NF-L subunit is its major ligand [12].
 

Analytical, diagnostic and therapeutic context of Myo5a

References

  1. Characterization of the molecular defects in Rab27a, caused by RAB27A missense mutations found in patients with Griscelli syndrome. Bahadoran, P., Busca, R., Chiaverini, C., Westbroek, W., Lambert, J., Bille, K., Valony, G., Fukuda, M., Naeyaert, J.M., Ortonne, J.P., Ballotti, R. J. Biol. Chem. (2003) [Pubmed]
  2. Expression of constructs of the neuronal isoform of myosin-Va interferes with the distribution of melanosomes and other vesicles in melanoma cells. da Silva Bizario, J.C., da Cunha Nascimento, A.A., Casaletti, L., Patussi, E.V., Chociay, M.F., Larson, R.E., Espreafico, E.M. Cell Motil. Cytoskeleton (2002) [Pubmed]
  3. Myosin Va and microtubule-based motors are required for fast axonal retrograde transport of tetanus toxin in motor neurons. Lalli, G., Gschmeissner, S., Schiavo, G. J. Cell. Sci. (2003) [Pubmed]
  4. Activation of myosin Va function by melanophilin, a specific docking partner of myosin Va. Li, X.D., Ikebe, R., Ikebe, M. J. Biol. Chem. (2005) [Pubmed]
  5. Identification of mRNA/protein (mRNP) complexes containing Puralpha, mStaufen, fragile X protein, and myosin Va and their association with rough endoplasmic reticulum equipped with a kinesin motor. Ohashi, S., Koike, K., Omori, A., Ichinose, S., Ohara, S., Kobayashi, S., Sato, T.A., Anzai, K. J. Biol. Chem. (2002) [Pubmed]
  6. Griscelli disease maps to chromosome 15q21 and is associated with mutations in the myosin-Va gene. Pastural, E., Barrat, F.J., Dufourcq-Lagelouse, R., Certain, S., Sanal, O., Jabado, N., Seger, R., Griscelli, C., Fischer, A., de Saint Basile, G. Nat. Genet. (1997) [Pubmed]
  7. Pigment cells: a model for the study of organelle transport. Nascimento, A.A., Roland, J.T., Gelfand, V.I. Annu. Rev. Cell Dev. Biol. (2003) [Pubmed]
  8. Direct interaction of microtubule- and actin-based transport motors. Huang, J.D., Brady, S.T., Richards, B.W., Stenolen, D., Resau, J.H., Copeland, N.G., Jenkins, N.A. Nature (1999) [Pubmed]
  9. Identification of an organelle receptor for myosin-Va. Wu, X.S., Rao, K., Zhang, H., Wang, F., Sellers, J.R., Matesic, L.E., Copeland, N.G., Jenkins, N.A., Hammer, J.A. Nat. Cell Biol. (2002) [Pubmed]
  10. Loss of heterozygosity at the dilute-short ear (Myo5a-Bmp5) region of the mouse: mitotic recombination or double non-disjunction? Favor, J., Neuhäuser-Klaus, A. Genet. Res. (1998) [Pubmed]
  11. Identification of a novel myosin-Va mutation in an ataxic mutant rat, dilute-opisthotonus. Futaki, S., Takagishi, Y., Hayashi, Y., Ohmori, S., Kanou, Y., Inouye, M., Oda, S., Seo, H., Iwaikawa, Y., Murata, Y. Mamm. Genome (2000) [Pubmed]
  12. Myosin Va binding to neurofilaments is essential for correct myosin Va distribution and transport and neurofilament density. Rao, M.V., Engle, L.J., Mohan, P.S., Yuan, A., Qiu, D., Cataldo, A., Hassinger, L., Jacobsen, S., Lee, V.M., Andreadis, A., Julien, J.P., Bridgman, P.C., Nixon, R.A. J. Cell Biol. (2002) [Pubmed]
  13. Rab27a is an essential component of melanosome receptor for myosin Va. Wu, X., Wang, F., Rao, K., Sellers, J.R., Hammer, J.A. Mol. Biol. Cell (2002) [Pubmed]
  14. Melanophilin and myosin Va track the microtubule plus end on EB1. Wu, X.S., Tsan, G.L., Hammer, J.A. J. Cell Biol. (2005) [Pubmed]
  15. The mouse neurological mutant flailer expresses a novel hybrid gene derived by exon shuffling between Gnb5 and Myo5a. Jones, J.M., Huang, J.D., Mermall, V., Hamilton, B.A., Mooseker, M.S., Escayg, A., Copeland, N.G., Jenkins, N.A., Meisler, M.H. Hum. Mol. Genet. (2000) [Pubmed]
  16. Melanophilin, the product of the leaden locus, is required for targeting of myosin-Va to melanosomes. Provance, D.W., James, T.L., Mercer, J.A. Traffic (2002) [Pubmed]
  17. Effects of some excitatory amino acid antagonists and drugs enhancing gamma-aminobutyric acid neurotransmission on pefloxacin-induced seizures in DBA/2 mice. De Sarro, G., Nava, F., Calapai, G., De Sarro, A. Antimicrob. Agents Chemother. (1997) [Pubmed]
  18. Gabapentin potentiates the antiseizure activity of certain anticonvulsants in DBA/2 mice. De Sarro, G., Spagnolo, C., Gareri, P., Gallelli, L., De Sarro, A. Eur. J. Pharmacol. (1998) [Pubmed]
  19. The actin-based motor myosin Va is a component of the acroplaxome, an acrosome-nuclear envelope junctional plate, and of manchette-associated vesicles. Kierszenbaum, A.L., Rivkin, E., Tres, L.L. Cytogenet. Genome Res. (2003) [Pubmed]
  20. Glutamate receptor targeting in the postsynaptic spine involves mechanisms that are independent of myosin Va. Petralia, R.S., Wang, Y.X., Sans, N., Worley, P.F., Hammer , J.A., Wenthold, R.J. Eur. J. Neurosci. (2001) [Pubmed]
  21. Ca2+-induced activation of ATPase activity of myosin Va is accompanied with a large conformational change. Li, X.D., Mabuchi, K., Ikebe, R., Ikebe, M. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  22. The actin-binding domain of Slac2-a/melanophilin is required for melanosome distribution in melanocytes. Kuroda, T.S., Ariga, H., Fukuda, M. Mol. Cell. Biol. (2003) [Pubmed]
  23. Identification of a minimal myosin Va binding site within an intrinsically unstructured domain of melanophilin. Geething, N.C., Spudich, J.A. J. Biol. Chem. (2007) [Pubmed]
  24. Human myosin-Vc is a novel class V myosin expressed in epithelial cells. Rodriguez, O.C., Cheney, R.E. J. Cell. Sci. (2002) [Pubmed]
  25. The acroplaxome is the docking site of Golgi-derived myosin Va/Rab27a/b- containing proacrosomal vesicles in wild-type and Hrb mutant mouse spermatids. Kierszenbaum, A.L., Tres, L.L., Rivkin, E., Kang-Decker, N., van Deursen, J.M. Biol. Reprod. (2004) [Pubmed]
  26. Slac2-a/melanophilin, the missing link between Rab27 and myosin Va: implications of a tripartite protein complex for melanosome transport. Fukuda, M., Kuroda, T.S., Mikoshiba, K. J. Biol. Chem. (2002) [Pubmed]
 
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